Advances in psychopharmacology : predicting and improving treatment response

338 Pages·2018·33.92 MB·English

by  Carman, John S., Gold, Mark S., Lydiard, R. Bruce

Advances in
Psychopharmacology :
Predicting and Improving
Treatment Response
Editors
Mark S. Gold, M.D.
Director of Research
Fair Oaks Hospital and
Psychiatric Diagnostic Laboratories
of America
Summit, New Jersey
R. Bruce Lydiard, Ph.D., M.D.
Associate Director of Research
Fair Oaks Hospital
Summit, New Jersey
John S. Carman, M.D.
Director of Research
Brawner Psychiatric Institute
Atlanta, Georgia
Boca Raton London New York
CRC PresCs isR anC im Pprrinets osf ,t hIenc.
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Library of Congress Cataloging-in-Publication Data
Main entry under title:
Advances in psychopharmacology.
Bibliography: p.
Includes index.
1. Psychopharmacology. 2. Psychology, Pathological—
Diagnosis. I. Gold, Mark S. II. Lydiard, R. Bruce.
III. Carman, John S. [DNLM: I. Psychotropic drugs—
Therapeutic use. 2. Dose-response relationship,
Drug. 3. Mental disorders—Drug therapy QV 77 A255]
RC483.A33 1984 615’.78 83-7695
ISBN 0-8493-5680-6
A Library of Congress record exists under LC control number: 83007695
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ISBN 13: 978-1-315-89043-2 (hbk)
ISBN 13: 978-1-351-06953-3 (ebk)
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INTRODUCTION
IMPROVING AND PREDICTING RESPONSE TO PSYCHOTROPIC
MEDICATIONS
The current generation fo widely effective psychotropic drugs were developed - often
fortuitously and always empirically - during the decade following World War 11. Most of
the subsequent 25 years have been spent ni generating and testing theories on the etiology
fo the major mental disturbances, based ni large part on their response to these agents.
Pharmacology provided both the impetus antdh e principal lines fo evidence for the dopamine
hypothesis of schizophrenia and the noradrenergic and indoleaminergic hypotheses fo mania
and depression.
Only ni recent years have a few groups fo investigators admitted a degree fo scientific
nihilism ni this search for etiologies and focused their explorations on a far more pragmatic
concern how to predict which subgroup fo patients with a particular psychiatric diagnosis
-
will respond to a particular pharmacological agent. Researchers had neglected clinicians and
clinical research issues for so long that few, fi any, groups were looking for ways to predict
response or improve response rate.
Admittedly the stability fo a given predictor is, over a period fo time, obfuscated by
changing diet, concurrent medications, compliance, etc. However, the potential rewards fo
finding accurate predictors have become increasingly obvious. First, there si a variable
latency period prior to behavioral response, and nearly a month at therapeutic blood levels
must pass before nonresponse can be categorically ascertained ni patients treated with neu-
roleptics, lithium, and antidepressants. Accordingly, accurate predictors fo which patient
will not respond would obviate ultimately ineffective drug trials that, yb delaying effective
treatment, would cost patients continued suffering, incapacitation, hospitalization expenses,
and risk fo harm to themselves or others. Second, 10 to 50% fo patients with primary
psychiatric illness who "respond" during open trials fo psychotropic drugs would have
responded equally well to placebo or recovered spontaneously. Growing awareness fo and
concern about iatrogenic morbidity of psychotropic drugs underscores the importance fo
selecting those patients ni whom a trial fo active drug would either be unnecessary or
ineffective. Studies should ideally correlate predictor variables withd rruegs ponse aass sessed
ni the same patient during na adequate double-blind placebo-crossover trial fo the agent ni
question. Response should be ascertained by such a design, with a control group receiving
only placebo (without a control group proposed, "predictors" fo lithium response utilizing
such behavioral measurements as the MMPI or SCL-90 may merely describe those patients
with a better natural course fi lefutn treated or thoser esponding tpol acebo). Third, corao llary
to prediction fo therapeutic response would be the prediction fo side effects (e.g., which
patients on neuroleptics might be especially likely to develop tardive dyskinesia, or which
manic patients on lithium might develop nephro- or neurotoxicity). Prevention (or mini-
mizing) fo side effects and maximizing therapeutic efficacy are increasingly possible in
clinical settings.
Drug trials in which a possible predictor is to be assessed must utilize valid and reliable
procedures to assess a clinically significant response and must administer the drug for an
adequate duration (e.g., 1 month for most neuroleptics or thymoleptics) and at adequate
dosages (e.g., 150 to 300 mglday for most tricyclics) commonly accepted as an "adequate"
trial. Ideally, any such study should be monitored not only by dosage but also by blood
levels in order to assure adequate absorption and compliance (e.g., HPLC or mass spectro-
metric assay fo tricyclic antidepressants, the radioreceptor assay for neuroleptics, platelet
MAO level for monoamine oxidase inhibitors, and atomic absorption or plasma emission
spectroscopy for lithium).
The ideal predictor of response should be readily available and rapidly and inexpensively
quantifiable, either before the patient begins treatment, or early (day l to 5) in the course
fo treatment. Symptom-descriptive predictors fo a behavioral response run particular risk fo
being redundant reiterations rather than true predictors; and when these are correlated with
response to an open trial, they run particular risk fo predicting the type of person responding
to placebo or remitting spontaneously.
We shaplrle sent data usingn euroendocrine testing( including tDheex amethasSounpep res-
sion and TRH tests), the RBCISerum ratio of lithium ion, Lithium Efflux, Platelet Serotonin
Transporter, and the cranial CT scan as predictors fo response to antidepressants, lithium,
and major tranquilizers, respectively. Before we begin with this exercise we will focus on
reducing heterogeneity in diagnostic groups. Improved medical and psychiatric diagnosis
by themselves reduce diagnostic heterogeneity and improve response of psychopharma-
cological treatment. Knowing homtwao k e psyac hiatric diagnosis (still to this day a diagnosis
fo exclusion)d emands a rigorous process which will be reviewed at great length. Thereafter
we will focus on the major medications used in general practice, family practice, and
psychiatry from the point of view of who should receive this medication and how we can
optimize response.
Psychiatrists have traditionally relied on the clinical interview to make diagnostic and
treatment decisions. As is true in other branches fo medicine, a careful andc omplete history
is fo utmost importance in evaluating the patient with psychiatric complaints. Over the last
01 to 51 years, however, the importance of clinical laboratory and diagnostic testing has
increased greatly. The psychiatrist of the 1980s and beyond will need to become familiar
with ther ecentd evelopments thiens e areas ni ordteor provide the safesta nd most efficacious
treatment possible for his or her patients.
There are several reasons for the burgeoning field fo diagnostic and laboratory testing.
Psychotropic drugs for the treatment of major depression, bipolar illness, schizophrenia, and
anxiety disorders are relatively effective and specific. Because of this, the need for accurate
diagnosis is increased. A number fo tests are available which allowp hysicians morec ertainty
ni clinical diagnosis, in the need for medication, and even ni the choice of a particular agent.
The response rate to some medications can be greatly improved fi blood levels are monitored
and dosages tailored for the individual patient. With the increased use fo drug treatment
comes thien creased prevalence of side effects. Lithium-induced thyroid raendndya slf unction
emphasizes the need for periodic medical evaluation; tardive dyskinesia highlights the im-
portance fo accurate diagnosis before exposing patients to the risk of potentially irreversible
damage. Psychiatry si now returning to its position as the subspecialty fo medicine, and
there si much interest ni the overlap between "medical" and "psychiatric" disorders, and
the subsequent questions ni differential diagnosis. An example is the interplay between
thyroid function and affective disorders. Finally, after years of neglect yb psychiatrists,
substance abuse is being recognized as an important disease complex and confounding factor
in psychiatric diagnosis. Advances such as GCIMS and radioimmunoassay procedures for
detection and quantification fo low drug levels help the physician recognize and treat the
substance abuser who may present with an affective or psychiatric syndrome. It is our hope
that this book will be a useful manual to physicians who are trying to reduce the risk and
maximize the benefits when prescribing psychopharmacologica1 treatments.
THE EDITORS
Mark S. Gold, M.D., si director fo research at Fair Oaks Hospital, Summit, N.J. He
holds similar positions with 800-Cocaine, Psychiatric Diagnostic Laboratories fo America,
ni Summit, New Jersey, and Regent Hospital, ni New York City. Dr. Gold alsoi s consultant
to the World Health Organization substance abuse program and the Yale University School
fo Medicine substance abuse unit.
Dr. Gold received his B.A. degree ni psychology in 1971 from Washington University,
in St. Louis, Missouri, and his doctor fo medicine ni 1975 from the University fo Florida
College fo Medicine, Gainesville. He became Neurobehavioral Fellow at Yale University
School fo Medicinea nd Chief Resident in the department fo psychiatry at the Yale University
School of Medicine. Thereafter, Dr. Gold served on the faculty of Yale University School
fo Medicine.
A Phi Beta Kappa, Dr. Gold was awarded the American Psychiatric Association Foun-
dation's Fund Annual Prize for his research in opiate addiction (1981-82). Dr. Gold was
the senior author on the discovery paper reporting the invention fo the first effective non-
opiate treatment for narcotics addicts in the history fo medicine (Patent No. 4,312,878). He
also received the 1982 Presidential Award from the National Association fo Private Psy-
chiatric Hospitals for his leadership in research and discoveries which have led to the
understanding, treatment, and prevention fo mental illness.
Dr. Gold si a member fo several professional organizations, including the American
Psychiatric Association, the Society of Neuroscience and the American Association for the
Advancement fo Science. He is also co-editor fo the Psychiatry Letter, Advances In Alcohol
and Substance Abuse and the International Journal of Psychiatry in Medicine, and serves
on the review board of several prestigious medical journals, including The Journal of the
American Medical Association and The American Psychiatric Association Journal.
Dr. Gold has lectured throughout the United States, and Eastern and Western Europe. He
hasa uthored or co-authored more than 200 papers, mainly dealing witthhr ee areas fo research
interest: identification and treatment fo drug abuse ni the work settindge;v elopment and use
fo biological measures in psychiatric diagnosis and treatment, and the use fo drug therapy
ni the treatment fo patients with depression. Dr. Gold teaches and lectures at universities
throughout the United States and Europe. He has lectured in England, Germany, Austria,
Sweden, France and the Netherlands in addition to lectures at Yale, Harvard, Brown,
Columbia, Cornell, Emory and other universities. Dr. Gold, in addition to this research and
clinical work, maintains an active schedule fo public service lectures to prevent drug abuse.
Dr. Gold has spoken at high schools throughout the New York-New Jersey-Connecticut
metropolitan area and appeared on national television shows such as 1ihP Donahue, John
Davidson, PM Magazine, Today Show, Good Morning America, and Dick Cavett, on the
subject of drug abuse and its prevention. Dr. Gold is the founder and Medical Director fo
800-Cocaine, the nation's first national cocaine Hotline. 800-Cocaine provides factual in-
formation about cocaine and its effects to cocaine users, parents, and concerned loved ones.
Dr. Gold and 800-Cocaine have been covered on ABC, NBC, and CBS network television
and radio as well as United Press, Associated Press, and Time Magazine.
Robert Bruce Lydiard, Ph.D., M.D., is Associate Director of Research at Fair Oaks
Hospital in Summit, New Jersey. Prior to joining the Fair Oaks Hospital staff, Dr. Lydiard
was Instructor in Psychiatry at Harvard Medical School and Attending Physician in the
Department fo Psychiatry at St. Elizabeth's Hospital, Boston. After receiving his B.A.
(psychology), Ph.D. (pharmacology), and (in 1977) his M.D. from the University of Min-
nesota in Minneapolis, Dr. Lydiard took his internship at Salem Hospital in Salem, Mas-
sachusetts, and his residency in psychiatry at Massachusetts General Hospital in Boston.
From to1 980 198 1, he was Chief Resident ni the Psychopharmacology Unit at Massachusetts
General, after which he received several research fellowships, including the Ethel Dupont-
Warren Fellowship Award ni Psychiatry (Harvard), a clinical and research fellowship( Mas-
sachusetts General), and a National Research Service Award (National Institute of Mental
Health). Dr. Lydiard's research centers on psychopharmacology and psychoneuroendocri-
nology, and includes work on biologic markers for affective disorders.
John Scott Carman, M.D., si Director, Adult Treatment Service, Brawner Psychiatric
Institute in Smyma, Georgia, and Clinical Assistant Professor in Psychiatry and Psycho-
pharmacology at Emory University in Atlanta, Georgia.
Dr. Carman graduated in 1967 from the University fo Notre Dame, Notre Dame, Indiana
with a B.S. degree ni Chemistry (magna cum laude). He obtained his M.D. degree in 1971
from the State University of New York Upstate ni Syracuse, where he was a New York
State Regents Scholar ni Medicine.
nI 1974 he completed his psychiatric residency at the University fo North Carolina at
Chapel Hill. From then until 1978, he was a clinical associate at the National Institute fo
Mental Health ni Bethesda, Maryland, and Washington, D.C.
From 1978 to 1981 he was na Associate Professor in Psychiatry at the University fo
Alabama in Birmingham where he was also Adult Inpatient Service Coordinator and Director
fo the Psychopharmacology Clinic.
Dr. Carman is a member fo the American Medical Association, American Psychiatric
Association, the Society of Biological Psychiatry and the International Society of
Psychoneuroendocrinology.
Among other awards, he has received the A. E. Bennett Award from the Society fo
Biological Psychiatry for outstanding clinical research in psychobiology and the Curt P.
Richter award from the International Society fo Psychoneuroendocrinology.
He is board certified in Psychiatry. He has presented over 03 lectures at national or
international meetings and has produced more than 70 publications in clinical psychobiologic
research. His current major research interests include biological predictors fo psychotropic
drug response and the influence fo calcium and calcitropic hormones on bipolar affective
disorder.
CONTRIBUTORS
John S. Carman, M.D. Carl L. Hamlin, M.D.
Director Associate Director,
Adult Treatment Service Outpatient Research Unit,
Brawner Psychiatric Institute Fair Oaks Hospital,
Summit, New Jersey; and
Atlanta, Georgia
Clinical Assistant Professor
Department fo Psychiatry
Charles Dackis, M.D.
UMD-Rutgers Medical School
Associate Director, Neuropsychiatric
Evaluation Services, New Jersey
Fair Oaks Hospital,
Summit, New Jersey; and
Instructor, Clinical Psychiatry, R. Bruce Lydiard, Ph.D., M.D.
Columbia Presbyterian Medical Center Associate Director of Research
New York, New York Fair Oaks Hospital
Summit, New Jersey
Todd kliW Estroff, M.D.
Assistant Director
Neuropsychiatric Evaluation Unit Robert Moreines, M.D.
Fair Oaks Hospital Assistant Director,
Summit, New Jersey Adult Inpatient Services
Fair Oaks Hospital
lrI Extein, M.D. Summit, New Jersey
Medical Director
Falkirk Hospital
Central Valley, New York H. Rowland Pearsall, M.D.
CO-DirectOourt,p atient Services
Frederick C. Goggans, M.D. Fair Oaks Hospital
Director, Neuropsychiatric Summit, New Jersey
Evaluation Service,
Psychiatric Institute of Fort Worth; and
A. L. C. Pottash, M.D.
Clinical Instructor,
Medical Director, Regent Hospital
Department fo Psychiatry,
(New York, New York);
University fo Texas Health Science
Medical Director, PANJ,
Center at Dallas
Fair Oaks Hospital (Summit, New Jersey);
Texas
Medical Director,
Mark S. Gold, M.D. Psychiatric Diagnostic Laboratories
Director fo Research of America;
Fair Oaks Hospital Psychiatrist-in-Chief, Falkirk Hospital
Summit, New Jersey (Central Valley, New York)
TABLE OF CONTENTS
DIAGNOSIS DNA TREATMENT RESPONSE
Chapter 1
Psychiatric Diagnosis: The State fo the Art.. ............................................. 1
Robert Moreines, Irl Extein, and Mark S. dloG
Chapter 2
Psychiatric Misdiagnosis ................................................................ 33
Todd W. Estroff and Mark .S Gold
Chapter 3
Thyroid Failure and Clinical Misdiagnosis .............................................. 67
Mark .S Gold and John .S Carman
PSYCHIATRIC MEDICATION DNA TREATMENT RESPONSE
Chapter 4
Antidepressants: Predicting ResponseiMaximizing Efficacy ............................. 83
Irl Extein, .A L. C. Pottash, Mark .S Gold, Richard Goggans, and R. Bruce Lydiard
Chapter 5
The Serotonin Subtype fo Depression .................................................. 107
Charles .A Dackis and Mark S. Gold
Chapter 6
Lithium: Predicting ResponseiMaximizing Efficacy .................................... 21 1
.R Bruce Lydiard and H. Rowland Pearsall
Chapter 7
MAO Inhibitors: Predicting ResponseIMaximizing Efficacy.. .......................... 157
Robert Moreines, and Mark .S Gold
Chapter 8
Antipsychotics: Predicting ResponseiMaximizing Efficacy ............................. 179
R. Bruce Lydiard, John .S Carman, and Mark .S Gold
Chapter 9
Anxiolytics: Predicting ResponseiMaximizing Efficacy.. .............................. ,225
Cary Hamlin and Mark .S Gold
SPECIAL CLINICAL PROBLEMS
Chapter 10
Alcoholism ............................................................................ .277
Charles .A Dackis and Mark .S Gold
Chapter 11
Narcotic Addiction .................................................................... ,289
Mark .S Gold, Charles .A Dackis, .A L. C. Pottash, and R. Bruce Lydiard
NOISULCNOC
Chapter 12
The Role fo the Laboratory in Psychiatry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .307
kraM S. Gold, A. L. C. Pottash, John S. Carman, and R. Bruce draidyL
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3 19